Abstract
Background. Enzyme Replacement Therapy (ERT) is the standard of care in Gaucher disease. The effects of withdrawal or reduced doses are debated, thus a retrospective cohort study was conducted to investigate clinical and laboratory differences in 34 Gaucher type 1 patients experiencing an ERT dosage reduction after the forced temporary imiglucerase shortage in 2009.
Methods. Haemoglobin concentration, leukocytes and platelets counts, and chitotriosidase activity were assessed at baseline and after 6 and 12 months (t0, t6, t12), while bone pain, energy, work or school performance, concentration, memory and social life every 3 months.
Results. The cohort was made up of 18 males and 16 females (medians: age 41.8 years, therapy duration 14.1 years, dosage reduction 35.5%). Haemoglobin, leukocytes and platelets remained substantially stable, while chitotriosidase activity showed an increase, especially after t6. Age, splenectomy or genotype were not associated with laboratory parameters changes, except for a significant median increase of chitotriosidase activity in non-splenectomised patients after 12 months (p = 0.01). At 3, 6, 9 and 12 months, more than 50% patients reported at least one problem in subjective well-being (56%, 65%, 70%, 58%, respectively), while bone pain occurred or worsened in 13/33, 13/32, 7/28 and 5/26 patients, respectively. No bone crises were reported.
Conclusions. Drug reduction did not induce substantial modification in the laboratory values but seems to have influenced the well-being perception of some Gaucher patients. Thus, bone pain, general health and quality of life should be carefully monitored during ERT reductions.
Competing interests: None declared
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Beutler E, Grabowski GA (2001) Gaucher disease. In: Scriver CR, Beaudet AL, Valle D, Sly WS, Childs B, Kinzler KW, Vogelstein B (eds) The metabolic & molecular bases of inherited disease. McGraw-Hill Medical Publishing Division, New York, pp 3635–3668
Czartoriska B, Tylki-Szymanska A, Lugowska A (2000) Changes in serum chitotriosidase activity with cessation of replacement enzyme (cerebrosidase) administration in Gaucher disease. Clin Biochem 33(2):147–149
Drelichman G, Ponce E, Basack N et al (2007) Clinical consequences of interrupting enzyme replacement therapy in children with type 1 Gaucher disease. J Pediatr 151:197–201
Elstein D, Abrahamov A, Hadas-Halpern I, Zimran A (2000) Withdrawal of enzyme replacement therapy in Gaucher’s disease. Br J Haematol 110:488–492
European Medicines Agency (EMEA) (2009) Supply shortages of Cerezyme and Fabrazyme – priority access for patients most in need of treatment recommended. Doc. Ref. EMEA/389995/2009. London, 25-6-2009
Giraldo P, Irun P, Alfonso P et al (2011) Evaluation of Spanish Gaucher disease patients after a 6-month imiglucerase shortage. Blood Cells Mol Dis 46:115–118
Goldblatt J, Fletcher JM, McGill J, Szer J, Wilson M (2011) Enzyme replacement therapy “drug holiday”: results from an unexpected shortage of an orphan drug supply in Australia. Blood Cells Mol Dis 46:107–110
Grinzaid KA, Geller E, Hanna SL, Elsas LJ II (2002) Cessation of enzyme replacement therapy in Gaucher disease. Genet Med 4(6):427–433
Hollak CEM, van Weely S, van Oers MHJ, Aerts JMFG (1994) Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease. J Clin Invest 93:1288–1292
Hollak CEM, vom Dahl S, Aerts JMFG et al (2010) Forze majeure: therapeutic measures in response to restricted supply of imiglucerase (Cerezyme) for patients with Gaucher disease. Blood Cells Mol Dis 44:41–47
Hughes DA, Pastores GM (2010) The pathophysiology of GD – current understanding and rationale for existing end emerging therapeutic approaches. Wien Med Wochenschr 160:594–599
Jmoudiak M, Futerman AH (2005) Gaucher disease: pathological mechanisms and modern management. Br J Haematol 129:178–188
Pastores GM, Weinreb NJ, Aerts H et al (2004) Therapeutic goals in the treatment of Gaucher disease. Semin Hematol 41(Suppl 5):4–14
Schwartz IVD, Karam S, Ashton-Prolla P et al (2001) Effects of imilglucerase withdrawal on an adult with Gaucher disease. Br J Haematol 113:1089
Vom Dahl S, Poll LW, Haussinger D (2001) Clinical monitoring after cessation of enzyme replacement therapy in M Gaucher. Br J Haematol 113:1084–1085
Zimran A, Altarescu G, Elstein D (2011) Nonprecipitous changes upon withdrawal from imiglucerase for Gaucher disease because of a shortage in supply. Blood Cells Mol Dis 46:111–114
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Additional information
Communicated by: Verena Peters
Appendices
Synopsis
Bone pain, general health and quality of life should be carefully monitored during ERT reductions.
Authors’ Contributions
LD participated in the study design, performed the statistical analysis and drafted the manuscript. AS participated in the study design and in the draft of the manuscript. AD carried out the chitotriosidase activity and genotype analyses and participated in the draft of the manuscript. DM acquired the data and participated in the draft of the manuscript. GL acquired the data and participated in the draft of the manuscript. GC participated in the design of the study. BB conceived the study, participated in its design and coordination and in the draft of the manuscript. All authors read and approved the final manuscript.
Competing Interests
The authors declare that they have no competing interests.
Rights and permissions
Copyright information
© 2012 SSIEM and Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Deroma, L. et al. (2012). Did the Temporary Shortage in Supply of Imiglucerase Have Clinical Consequences? Retrospective Observational Study on 34 Italian Gaucher Type I Patients. In: Brown, G., Morava, E., Peters, V., Gibson, K., Zschocke, J. (eds) JIMD Reports - Case and Research Reports, 2012/4. JIMD Reports, vol 7. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2012_158
Download citation
DOI: https://doi.org/10.1007/8904_2012_158
Received:
Revised:
Accepted:
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-32441-3
Online ISBN: 978-3-642-32442-0
eBook Packages: MedicineMedicine (R0)